Serotonin signal transduction in two groups of autistic patients

While several classifications of autistic children are extant, one is the division into two groups, with high or low repetitive behaviors (Insistence on Sameness--IS). At least a subset of the high IS group also show elevated serotonin (5HT) in their platelets. The relationship between this elevated serotonin and the behavior of these children has not been explored. Tools to make such an exploration are wanting, as it is difficult to access tissue outside of blood and often such tissue does not yield much information on the altered brain chemistry of autistic patients. It is noteworthy that drugs used to treat autistic children are intimately involved with serotonin, as they are either agents that inhibit serotonin uptake into cells (SSRIs) or agents that antagonize serotonin effects at the 5HT2a receptor (atypical antipsychotics). Lymphocytes have been collected from children with high and low IS and high and low platelet serotonin. These cells have been treated with a virus, which "immortalizes" the cells and allows them to be grown in culture. These cells are used normally as a source of DNA for genetic studies, which, while having yielded a great deal of important information, have not helped us to understand the relationship of serotonin to IS. Fortunately, these cells can also be used for pharmacology/cell biology, and we intend to grow the cells and examine differences in serotonin signaling among cells from different patients. By comparing lymphoblasts from the high- and low-IS and high and low serotonin subjects, we hope to develop a clearer understanding of serotonin signaling in autism. Since many of the current drugs for autism influence the serotonin signaling system, it is thought that such an improved understanding will help us to develop more individualized therapy for these children and develop improved medications.